This parasitologic research project is designed to investigate the phenomena of vitellogenesis and the subsequent immunologic response to the products of vitellogenesis in vitro. Preliminary studies have indicated the feasibility of maintenance of viable pairs of S. mansoni in vitro with resultant vitellogenesis, proceeding for periods of up to 4 weeks. The in vitro culture conditions also permit the survival of a variety of subpopulations of mononuclear cells and allows their specific sequential interaction with the products of vitellogenesis. These initial studies have suggested a pattern of reactivity which is highly analogous to granuloma formation, a cell-mediated immunological response. It is the intend of this proposal to: 1) Define the quantitative and qualitative evolution of vitellogenesis and granuloma formation as reflected in the in vitro models; 2) Determine the effect of cells and their soluble products, obtained from previously immunized hosts, upon vitellogenesis in vitro; 3) Elucidate the subpopulations of cells and their soluble products which interact to produce the phenomena of granuloma formation; 4) Determine the feasibility of utilizing this in vitro system to assess in a quantitative manner host immunity and mode of action of immunogens and drugs in influencing vitellogenesis and granuloma formation. Specific attention will be paid to those mechanisms which are operative in the manifestation of optimal immunologically mediated resistance to the phenomenon of vitellogenesis, and to those processes which are germane to the modulation of subsequent granuloma formation. Since host morbidity is due primarily to an adverse immune response to the products of vitellogenesis, these studies will provide valuable information relative to the goal of control of host morbidity while preserving immunologically mediated resistance.